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Mitochondrial interactome quantitation reveals structural changes in metabolic machinery in the failing murine heart

ABSTRACT: Advancements in cross-linking mass spectrometry (XL-MS) for structural analysis of proteins bridge the gap between purified systems and native tissue environments. Here, isobaric quantitative protein interaction reporter technology (iqPIR) was utilized to further extend XL-MS to the first system-wide comparative study of mitochondrial proteins from healthy and diseased murine hearts. The failing heart interactome includes 588 statistically significant cross-linked peptide pairs altered in the disease condition. Structural insight into ketone-oxidation metabolons, OXPHOS machinery, and nucleotide transporter hybrid-conformations support mitochondrial remodeling in failing hearts while bringing forth new hypotheses for pathological mechanisms. The application of quantitative cross-linking technology in tissue provides molecular-level insight into complex biological systems challenging to model in cell culture, thus providing a valuable resource for studying human diseases.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Heart

SUBMITTER: Xiaoting Tang

LAB HEAD: James E Bruce

PROVIDER: PXD035622 | Pride | 2022-08-02

REPOSITORIES: pride

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			Action	DRS
	040522_0316_7_sham_2h_1.index	Other
	040522_0316_7_sham_2h_1.raw	Raw
	040522_0316_7_sham_2h_2.index	Other
	040522_0316_7_sham_2h_2.raw	Raw
	040522_0317_11_Tac_2h_1.index	Other

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Mitochondrial interactome quantitation reveals structural changes in metabolic machinery in the failing murine heart

Project description:Advancements in cross-linking mass spectrometry (XL-MS) for structural analysis of proteins bridge the gap between purified systems and native tissue environments. Here, isobaric quantitative protein interaction reporter technology (iqPIR) was utilized to further extend XL-MS to the first system-wide comparative study of mitochondrial proteins from healthy and diseased murine hearts. The failing heart interactome includes 588 statistically significant cross-linked peptide pairs altered in the disease condition. Structural insight into ketone-oxidation metabolons, OXPHOS machinery, and nucleotide transporter hybrid-conformations support mitochondrial remodeling in failing hearts while bringing forth new hypotheses for pathological mechanisms. The application of quantitative cross-linking technology in tissue provides molecular-level insight into complex biological systems challenging to model in cell culture, thus providing a valuable resource for studying human diseases.

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